Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women (ProliaHip)

Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women: a Randomized, Double-blind, Placebo-controlled Study

This randomized clinical trial will evaluate the efficacy of an antiresorptive osteoporosis drug (denosumab) in prevention of periprosthetic bone loss and in promotion of implant osseointegration (bone bonding) in postmenopausal women after total hip replacement. The investigators assume that denosumab prevents periprosthetic bone loss and enhances bone bonding of the hip stem in postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Hip Osteoarthritis
• Intervention / Treatment: Drug: Denosumb; Drug: Placebo (for denosumab)

Detailed Description

This is a randomized, double-blind and placebo-controlled trial to evaluate the efficacy of denosumab on the biologic incorporation of cementless hip prosthesis. The study population consists of sixty-eight postmenopausal female patients, who are scheduled to have cementless total hip replacement (THA) for primary hip osteoarthritis. The patients will be randomly assigned to receive a subcutaneous injection of denosumab 60 mg or placebo four weeks before surgery and 22 weeks after surgery. The primary hypothesis is that denosumab is effective in preventing periprosthetic bone loss in the proximal femur as measured by DXA. The secondary hypothesis is that denosumab is effective in enhancement of bone bonding (osseointegration) of cementless femoral stems, as measured by model-based radiostereometric analysis.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20521
    • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women, age: ≥ 60 years to ≤ 85 years at randomization
• Degenerative primary hip osteoarthritis as the indication of hip replacement
• Signed informed consent

Exclusion Criteria:

• Presence of severe osteoporosis (T-score less than -4.0 and a previous fracture)
• Presence of Dorr C-type geometric change of the proximal femur
• Evidence of secondary osteoporosis
• Clinical or laboratory evidence of hepatic disease
• Laboratory evidence of hypocalcaemia
• Vitamin D deficiency (serum 25-OH(D) < 12 ng/mL)
• Disorders of parathyroid function
• Uncontrolled hyperthyroidism or hypothyroidism
• History of malignancy, radiotherapy or chemotherapy for malignancy (except basal cell carcinoma of the skin) within the last 5 years
• History of osteonecrosis of the jaw
• History of recent tooth extraction or other dental surgery and/or invasive dental work planned in the next 2 years
• Severe asthma or chronic obstructive pulmonary disease
• History of solid organ or bone marrow transplant

• Use within 12 months of drugs that affect bone metabolism such as ant-osteoporotic agents (including SERMS), estrogens, testosterone, and anti-epileptics:

  • Cumulative dose of 500 mg prednisone or equivalent within the last 6 months
  • Ever use of oral or iv bisphosphonates
  • Ever use of strontium ranelate or fluoride

• Use of the following medications:

  • chronic systemic ketoconazole
  • androgens
  • cinacalcet
  • aluminum
  • lithium
  • protease inhibitors
  • gonadotropin-releasing hormone agonists
• Rheumatoid arthritis or any other inflammatory arthritis
• History of skeletal disorder, such as Paget's disease or osteomalacia
• Alcohol abuse

• General

  • Mental, neurological or other conditions that may affect the ability to perform functional or clinical assessments required by the protocol
  • Subjects with known sensitivity or intolerance to any of the products to be administered (calcium and D-vitamin supplements, denosumab)
  • Subject will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge
  • Any other condition that, in the judgement of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab; Subcutaneous injection of denosumab 60 mg 4 weeks before surgery and 22 weeks after surgery	Drug: Denosumb; Prefilled syringe of 1 mL denosumab solution; Other Names: Brand name: Prolia
Placebo Comparator: Placebo; Subcutaneous injection of placebo 4 weeks before surgery and 22 weeks after surgery	Drug: Placebo (for denosumab); Other Names: Prefilled syringe of 1 mL placebo solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periprosthetic bone mineral density (BMD)	Periprosthetic BMD of the proximal femur will be measured according to seven Gruen zones and compared with the baseline value	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiostereometric analysis (RSA) of prosthesis stem migration	The translatory and rotatory migration of the femoral stem will be measured by means of model-based RSA and compared with the position at the baseline	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional recovery	To investigate if the enhanced incorporation of hip prostheses in denosumab treated patients compared to placebo leads to faster functional recovery as measured by main parameters of gait analysis, pedometer evaluation of walking activity and patient reported outcome measures	48 weeks

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: Amgen
• Investigators: Principal Investigator: Hannu T Aro, MD, PhD, Turku University Hospital

Publications and helpful links

General Publications

• Aro HT, Alm JJ, Moritz N, Makinen TJ, Lankinen P. Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women: a 2-year RSA study of 39 patients. Acta Orthop. 2012 Apr;83(2):107-14. doi: 10.3109/17453674.2012.678798. Epub 2012 Apr 11.
• Moritz N, Alm JJ, Lankinen P, Makinen TJ, Mattila K, Aro HT. Quality of intertrochanteric cancellous bone as predictor of femoral stem RSA migration in cementless total hip arthroplasty. J Biomech. 2011 Jan 11;44(2):221-7. doi: 10.1016/j.jbiomech.2010.10.012. Epub 2010 Nov 11.
• Alm JJ, Makinen TJ, Lankinen P, Moritz N, Vahlberg T, Aro HT. Female patients with low systemic BMD are prone to bone loss in Gruen zone 7 after cementless total hip arthroplasty. Acta Orthop. 2009 Oct;80(5):531-7. doi: 10.3109/17453670903316801.
• Makinen TJ, Alm JJ, Laine H, Svedstrom E, Aro HT. The incidence of osteopenia and osteoporosis in women with hip osteoarthritis scheduled for cementless total joint replacement. Bone. 2007 Apr;40(4):1041-7. doi: 10.1016/j.bone.2006.11.013. Epub 2007 Jan 17.
• Makinen TJ, Koort JK, Mattila KT, Aro HT. Precision measurements of the RSA method using a phantom model of hip prosthesis. J Biomech. 2004 Apr;37(4):487-93. doi: 10.1016/j.jbiomech.2003.09.004.
• Nazari-Farsani S, Finnila S, Moritz N, Mattila K, Alm JJ, Aro HT. Is Model-based Radiostereometric Analysis Suitable for Clinical Trials of a Cementless Tapered Wedge Femoral Stem? Clin Orthop Relat Res. 2016 Oct;474(10):2246-53. doi: 10.1007/s11999-016-4930-0. Epub 2016 Jun 22.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): February 4, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: August 16, 2013
• First Submitted That Met QC Criteria: August 19, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): April 30, 2018
• Last Update Submitted That Met QC Criteria: April 26, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Osteoarthritis; Osteoporosis; Hip replacement; Denosumab; Radiostereometric analysis (RSA); Dual energy X-ray absorptiometry (DXA)
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Hip; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: ISS 20109714; 2011-000628-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes